Innate immunity and cardiac allograft rejection

MGH Transplant Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kidney international. Supplement 12/2010; 119(119):S18-21. DOI: 10.1038/ki.2010.417
Source: PubMed


The development of immunosuppressive drugs to control adaptive immune responses has led to the success of heart transplantation as a therapy for end-stage heart failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained clinical significance as mounting evidence now indicates that innate immune responses have important roles in the acute and chronic rejection of cardiac allografts including cardiac allograft vasculopathy (CAV). Whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and in the development of CAV. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection. Finally, new data indicate that activation of complement is linked to acute rejection and CAV. In summary, the conventional wisdom that the innate immune system is of little importance in whole-organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, and complement will be necessary to prevent CAV completely and to eventually achieve long-term tolerance to cardiac allografts.

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    • "Although immunosuppressive drugs permit successful heart transplantation, they do not always prevent chronic rejection. Innate immune responses like infiltration by NK cells, activation of Toll-like receptors (TLR), and complement deposition are known to participate in the acute rejection of cardiac allografts and in the development of CAV [98]. The involvement of complement in graft rejection was first suggested in 1999, when Baldwin et al. found deposition of C4d and C3 in a series of cardiac biopsy specimens in the first weeks after transplantation and demonstrated that this deposition was associated with the peritransplant ischaemic injury [99]. "
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